Efficacy and safety of dexmedetomidine in peripheral nerve blocks: A meta-analysis and trial sequential analysis

BACKGROUNDThe duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, several additives, including dexmedetomidine (DEX), have been investigated in order to prolong postoperative analgesia following single-shot regional anaesthesia.OBJECTIVESThe aim of this meta-analysis was to assess the efficacy and safety of the addition of perineural DEX to local anaesthetics compared with local anaesthetics alone or local anaesthetics combined with systemic administration of DEX.DESIGNA systematic review of randomised controlled trials (RCT) with meta-analysis, trial sequential analysis and assessment of the quality of evidence by the GRADE approach.DATA SOURCESThe databases MEDLINE, CENTRAL and EMBASE (to May 2017) were systematically searched.ELIGIBILITY CRITERIAAll RCTs investigating the efficacy and safety of perineural DEX combined with local anaesthetics compared with local anaesthetics alone or local anaesthetics in combination with systemic DEX in peripheral nerve blocks of adults undergoing surgery were included.RESULTSA total of 46 RCTs (3149 patients) were included. Patients receiving perineural DEX combined with local anaesthetics had a longer duration of analgesia than local anaesthetics alone [mean difference 4.87h; 95% confidence interval (95% CI) 4.02 to 5.73; P<0.001; I-2=100%; moderate-quality evidence]. The most important adverse events in the DEX group were intraoperative bradycardia [risk ratio 2.83; 95% CI 1.50 to 5.33; P=0.035; I-2=40%; very low-quality evidence] and hypotension (risk ratio 3.42; 95% CI 1.24 to 9.48; P=0.002; I-2=65%; very low quality evidence). In contrast, there were no differences in the duration of analgesia between perineural or intravenous DEX combined with local anaesthetics (mean difference 0.98h; 95% CI -0.12 to 2.08; P=0.08; I-2=0%).CONCLUSIONThis meta-analysis demonstrated that DEX in combination with local anaesthetics increases postoperative analgesia for around 5h. However, there are higher risks of intraoperative hypotension and bradycardia. Findings on side effects are associated with high uncertainty. Initial evidence suggests no difference in the duration of analgesia associated with systemic or perineural DEX.TRIAL REGISTRATIONCRD42016042486